Several cases of neurological disease in dogs after
poisoning by food- and feed-borne Penicillium toxins in Norway during the last years have uncovered a lack of knowledge regarding the toxicity and mechanism of action of neuroactive
mycotoxins. In the present study, the lowest
tremor-inducing dose after single
oral administration of
penitrem A to mice was 0.50 mg/kg bw. The estimated half maximal effective dose (ED(50)) in respect to the visual
tremor scale was 2.74 mg/kg bw. Mice receiving the maximum
penitrem A dose (8 mg/kg bw) suffered severe spontaneous
tremors and even convulsions.
Thomitrem A and E are
penitrem analogues lacking the C-16-C-18
ether linkage and possessing an
olefin at C-18-C-19. Compared with
penitrem A, the lowest
tremor-inducing dose of
thomitrem A was 16-times higher (8 mg/kg bw) and
thomitrem E was found to be non-tremorgenic at the highest dose tested (16 mg/kg bw). During a recovery phase of two weeks post administration animals appeared restored and no changes in feeding and other biological processes were observed. An initial dose-related
weight reduction was observed 2 days after
penitrem A administration.
Penitrem A was absorbed and distributed to gastrointestinal tract, liver, kidneys and brain in the mice. Elimination of
penitrem A appeared to be mainly hepatic and the highest concentration levels were found 1 h post administration for all investigated organs. The relationship between liver and gastrointestinal tract concentration levels showed time-dependent linear correlation and a doubling within 1.5 h.